TY - JOUR
T1 - Altered autoantigen structure in Sjögren's syndrome
T2 - Implications for the pathogenesis of autoimmune tissue damage
AU - Rosen, A.
AU - Casciola-Rosen, L.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2004
Y1 - 2004
N2 - The etiology and pathogenic mechanisms underlying Sjögren's syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet.
AB - The etiology and pathogenic mechanisms underlying Sjögren's syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet.
KW - Apoptosis
KW - Autoantibody
KW - Autoantigen
KW - Autoimmunity
KW - Caspase
KW - Granzyme B
KW - Protease
KW - Structure
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U2 - 10.1177/154411130401500304
DO - 10.1177/154411130401500304
M3 - Review article
C2 - 15187033
AN - SCOPUS:3042778439
SN - 1045-4411
VL - 15
SP - 156
EP - 164
JO - Critical Reviews in Oral Biology and Medicine
JF - Critical Reviews in Oral Biology and Medicine
IS - 3
ER -